Abouhashem Nehal S, Elwan Amira, Elaidy Noha F
Departments of Pathology.
Clinical Oncology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
Appl Immunohistochem Mol Morphol. 2022;30(5):e40-e49. doi: 10.1097/PAI.0000000000001017. Epub 2022 Mar 14.
Squamous cell carcinoma of the head and neck (HNSCC) is recognized as the third most common cause of death. Incomplete resection of the primary tumor is the main cause of local recurrence and poor prognosis in HNSCC. Histologic assessment in order to determine "tumor-free" margins could be inadequate because of malignant transformation occurs at the molecular level earlier than the morphologic level. The present study aimed to evaluate the prognostic significance of eukaryotic initiation factor 4E (eIF4E) and Osteopontin in the tumor cells and histologically tumor free surgical margins of HNSCC. This cohort study was performed on 60 cases of HNSCC diagnosed at the Department of Pathology and treated at the Clinical Oncology Department, Faculty of Medicine, Zagazig University. Our enrolled formalin fixed paraffin embedded biopsy specimens with their matched tumor free surgical margins from resected head and neck squamous cell carcinoma were immunostaind for eIF4E and Osteopontin markers. 65% of our HNSCC patients had eIF4 E positive cytoplasmic immunostaining and 70% of them exhibited Osteopontin staining. Two-thirds of the dead patients exhibited high Osteopontin positive staining, whereas the surviving group did not exhibit this high expression. Concerning eIF4E, 85% and 5% of the dead patients showed high and low eIF4E expression, respectively. Disease-free survival (DFS) and overall survival were significantly (P=0.000) different between high and negative expression of Osteopontin, high and negative expression of eIF4E. 84% of patients with eIF4E positive margins and 75% with Osteopontin positive margins had local recurrence. In addition, negative expression of eIF4E is associated with highly significant better DFS and overall survival (P=0.000 and 0.001), respectively, in the margin negative expression status, while negative expression of Osteopontin was significantly associated with better DFS but of no significance in overall survival outcome. Our findings suggest that tumor-free surgical margins in HNSCC may be redefined as histologically Osteopontin and eIF4E negative resection margins. However, multicenter prospective studies are required to further evaluate their clinical utility in the surgical management of primary HNSCC.
头颈部鳞状细胞癌(HNSCC)被认为是第三大常见死因。原发性肿瘤切除不完全是HNSCC局部复发和预后不良的主要原因。由于恶性转化在分子水平早于形态学水平发生,因此用于确定“无肿瘤”切缘的组织学评估可能并不充分。本研究旨在评估真核起始因子4E(eIF4E)和骨桥蛋白在HNSCC肿瘤细胞及组织学上无肿瘤手术切缘中的预后意义。这项队列研究对60例在扎加齐格大学医学院病理科诊断并在临床肿瘤科治疗的HNSCC病例进行。我们纳入了来自切除的头颈部鳞状细胞癌的福尔马林固定石蜡包埋活检标本及其匹配的无肿瘤手术切缘,对其进行eIF4E和骨桥蛋白标记物的免疫染色。65%的HNSCC患者eIF4E细胞质免疫染色呈阳性,其中70%表现出骨桥蛋白染色。三分之二的死亡患者骨桥蛋白阳性染色较高,而存活组未表现出这种高表达。关于eIF4E,85%和5%的死亡患者分别表现出高和低的eIF4E表达。骨桥蛋白高表达与阴性表达、eIF4E高表达与阴性表达之间的无病生存期(DFS)和总生存期存在显著差异(P = 0.000)。eIF4E切缘阳性的患者中有84%、骨桥蛋白切缘阳性的患者中有75%发生局部复发。此外,在切缘阴性表达状态下,eIF4E阴性表达分别与显著更好的DFS和总生存期相关(P = 0.000和0.001),而骨桥蛋白阴性表达与更好的DFS显著相关,但对总生存结果无显著意义。我们的研究结果表明,HNSCC的无肿瘤手术切缘可在组织学上重新定义为骨桥蛋白和eIF4E阴性的切除切缘。然而,需要多中心前瞻性研究来进一步评估它们在原发性HNSCC手术管理中的临床效用。